Phototherapy, defined herein as the use of light in the treatment of tissue in the human body, is a well established field of medicine. Light, defined as electromagnetic radiation of one or more wavelengths, may be used as the sole component of phototherapy, or phototherapy may involve the combination of light with drugs, dyes or other chemical agents, as well with radiofrequency, ultrasound, or other forms of energy. Phototherapy may also involve a combination of tissue temperature modification with the application of light, most frequently in the form of surface cooling. Many of the most important applications of phototherapy involve ablation, coagulation, denaturation or other heat-induced changes in the tissue.
In phototherapy, it is often desirable to expose an area of tissue to treatment. For example, it may be desirable to illuminate a surface area of the skin to treat a multitude of hair follicles associated with unwanted hair. It is often desirable that the area of tissue be exposed to light of substantially uniform distribution. These objectives of area irradiation and uniformity of distribution have been accomplished by reimaging the exit face of an optical fiber onto the tissue surface. Optical fibers are a commonly used transmission system for lasers. Handpieces designed to reimage the exit face of an optical fiber connected to a laser are well known in phototherapy, and design principles have been described (e.g., Hunter et al., Proc. SPIE Vol. 2993, pages 168-179, 1997). Such handpieces typically include at least two lenses disposed along an axis orthogonal to the surface to be irradiated. Because the fiber face has a very small area, a large magnification may be required for phototherapy of a large surface area. Consequently, handpieces commonly have a long axial length, typically of several centimeters, between the exit face of the optical fiber and the tissue surface to be exposed to light.
An example handpiece 1 is shown schematically in FIG. 1, where an optical fiber 2 is attached at one end to a light source (not shown) and at or near the other end by a connector 2a to the handpiece 1 comprising a cylindrical housing 4 that holds two plano-convex lenses 3 selected to reimage the exit face of the fiber 2b. The housing has an open end with a standoff 4a of a length that allows the handpiece to be positioned in contact with the tissue surface so that the light is substantially uniformly distributed over a circular area 5 at or near the image plane on the tissue surface. The axial length of the handpiece orthogonal to the tissue surface is very large compared to the diameter of the irradiated area of the tissue. To avoid light losses, the lenses and windows of the handpiece may be anti-reflection (AR) coated for the wavelength of the light source. A particular AR coating is effective over a limited range of wavelengths, consequently a handpiece may not be compatible with different light sources.
In some phototherapy handpieces, reimaging of the fiber exit face may be approximate, to reduce the axial length. Simpler phototherapy handpieces may have no lens or one lens, although the light distribution may have poor uniformity. In some cases, the handpiece may have the capability of cooling the treatment site, for example by transmitting the light from a source through a cooled window or lens in thermal contact with the treatment site, or by emitting a spray of cooling fluid onto the treatment site. The light passing through and emitted from a phototherapy handpiece may be substantially collimated, divergent or convergent, such that it travels approximately parallel to the long axis of the handpiece and approximately orthogonal to the tissue surface. Commercially available examples of phototherapy handpieces of this directed output type include the GentleLase and Vbeam laser handpieces produced by Candela Corporation (Wayland, Mass.) for removal of hair, and for treatment of cutaneous vascular lesions and aging skin, respectively.
Such handpieces require care on the part of the operator to maintain their orientation perpendicular to the treatment surface, for adequate uniformity of light distribution and tissue cooling. Furthermore, because of the diameter of the optics and length of their housing, as well as other components, for example tissue cooling systems, these handpieces are bulky, heavy, and may be awkward to hold. Operators frequently experience fatigue when performing long procedures. Furthermore, when employing active cooling for protection of superficial tissue layers from the effects of higher power light sources, it is necessary to use recirculating chillers, cryogen spray devices, thermoelectric coolers, cold air machines, and the like. These active cooling devices add cost and complexity, and in some cases use consumables, such as cryogen and gases.
Despite these known disadvantages of large, bulky handpieces, devices of this type continue to be in widespread use, particularly in dermatologic phototherapy, where uniformity of emitted light distribution is important. Fluences of a few to 100 J/cm2 or higher can readily be achieved at the tissue surface, which makes these devices appropriate for relatively high power phototherapeutic procedures that involve ablating, coagulating, denaturing or otherwise thermally injuring tissue or tissue components. Such procedures may be highly efficacious. When pulse durations on the order of a few to hundreds of milliseconds are used, peak irradiances produced by these devices at the tissue surface may range up to several thousand W/cm2 or higher. Bulky handpieces in present use can be designed to withstand high powers.
Phototherapy handpieces of the above-described type produce light of relatively uniform directionality. It is recognized that this directed output can readily damage the cornea or retina of the eye, and requires the use of eye protection by both operator and patient. Recently, phototherapy devices that emit diffuse light output have been described, as a means of providing increased eye safety. For example, Grove et al. (U.S. Pat. No. 7,452,356) have described a device with a hollow chamber or passageway through which light travels from a source, to an optical diffuser at the distal end. If light is accidentally emitted when directed towards the eye, the energy density at the eye will be low because of the scattered and highly divergent output of the handpiece.
In Weckwerth et al. (US 2006/0009749), light from a source is transmitted through opposing surfaces of a solid transparent light guide to an optical diffuser at the distal end of a handpiece. Alternatively, light may enter the light guide through a reflective diffuser, or the light guide itself may have diffusing input or output surfaces. Light propagates in a substantially forward direction through the light guide, that is, in a direction orthogonal to the tissue surface. These diffusing handpiece devices of Grove et al. and Weckwerth et al. provide enhanced eye safety, compared to phototherapy handpieces emitting directed light, and may contain a light source within the housing of the handpiece such that the entire apparatus is handheld. However, the direction of overall light propagation remains orthogonal to the tissue surface in these diffusing devices, and the handpieces are therefore still bulky and large compared to the dimension of the irradiated area on the tissue surface, and consequently have the disadvantages of the previously described phototherapy handpieces.
An example of a diffusing type device described by Weckwerth et al. (US 2006/0009749) is depicted schematically in FIG. 2. Light from an optical fiber (2) attached at one end to a light source (not shown) and at the other end to a reflective back surface (6), travels by total internal reflection (TIR) in a substantially forward direction through an elongated, slightly tapered light guide (7). Upon exiting the light guide, also in a substantially forward direction, the light impinges on optical diffuser (8) and is emitted through a window (9). Any portion of light reflected backwards at the light guide exit surface is reflected at back surface (6) and redirected in the forward direction again through the light guide. With proper design of the light guide and other optical components, the output distribution at the window may be substantially uniform. Since the light is scattered by the diffuser, the output will be low unless the surface to be irradiated is in contact with the window. The device described by Weckwerth et al. is intended to be used with the window in contact with the tissue to be treated. The dimensions of the irradiated area (5) are those of the output window (9).
In US 2007/0032847, Weckwerth et al. described a diffusing type device having a hollow chamber with reflective walls instead of a light guide. The length of the hollow chamber is 1 to 2 times the length of the output window on the device, for adequately uniform light distribution, according to the description in this application of Weckwerth et al.
A phototherapy device of the diffusing type is commercially available from TRIA Beauty (Pleasanton, Calif.). This device is a cordless handheld unit containing battery and light source that has been FDA cleared for hair removal. The overall dimensions of the TRIA device are large compared to the dimension of the output window, and active skin surface cooling technology such as fluid flow or cryogen spray, which would have further added to the weight and power requirements, is not incorporated into the device. The TRIA device produces a maximum irradiance of about approximately 30 W/cm2 from a laser source operating at 800 nm. Without active skin cooling, the TRIA is limited to use by people with light skin and without suntans.
In other phototherapy applications, an array of light generating sources may be disposed over the tissue to provide irradiation of an area. Leber et al. (U.S. Pat. No. 6,860,896) described a device comprising a plurality or array of light-emitting diodes (LEDs) on a substrate, which can be brought in contact with the skin so that when the LEDs are sequentially activated the light traces acupuncture meridians, for a characteristically low power biostimulation effect. Russell (U.S. Pat. No. 6,290,713) has described a flexible low power illuminator using an array of LEDs surrounded by coolant channels to dissipate heat and prevent heat transfer to the treatment surface, and scattering elements such as bubbles, particles, or paint dots disposed between the light sources and the treatment surface to homogenize the distribution of light from the plurality of emitters. The device may be placed in contact with skin for phototherapy, and produces an average irradiance described as preferably at least 50 milliwatts/cm2. An array of diode lasers disposed in a flexible bandage or implantable disc and electrically connected to a power supply has been described by Prescott (WO 98/43703) for low level laser irradiation to stimulate healing of myocardium.
An array of sources overlying the treatment site may provide a means of performing phototherapy with a relatively thin, low profile optical assembly. The source array approach is currently limited to low power applications, however, such as biostimulation. Other disadvantages of the source array approach are complexity, the need for electrical connection to each source, management of waste heat generated by the light sources in proximity to the treatment surface, and the potential hazards of electrical current in proximity to the treatment surface and of explosive failure of the light generating sources. Therapeutic applications of the source array approach are limited by relatively low powers produced by the arrays.
Another approach involves the use of fiber optic mats or patches made of woven optical fibers, where bends in the optical fibers serve as regions of light leakage. The average irradiance that can be achieved at the mat surface is low. Yet another approach is to produce light inside a thin layer that can be disposed over the treatment site, for example by electroluminescence (Holloway et al. (U.S. Pat. No. 7,304,201)) or chemiluminescence (Zelickson et al. (US 2005/0080465)). These approaches are also significantly limited in output power.
Therefore, despite the numerous devices and methods for applying light to an area of tissue using handpieces, arrays, patches, and light guides, there remain substantial long-standing limitations. The available devices for uniformly irradiating surface areas of tissue are large and bulky when capable of high power treatment. Thin, flat, low profile devices of the prior art, which may include some flexible patches, mats, and arrays, are limited to low power applications. The low power limitation of the low profile optical assemblies of the prior art precludes their use for ablation, coagulation, denaturation, or other thermal modification of tissue. This limitation of the prior art low profile devices precludes many of the most effective and well established phototherapeutic treatments, such as hair removal, vascular lesion eradication, pigmented lesion eradication, acne treatment, tattoo treatment, scar treatment, and many others.
For treatments that involve irradiation of superficial tissue of a lumen or hollow organ of the body, current technology also has significant limitations. Light can be delivered using an optical fiber positioned within the lumen and irradiating over a wide range of angles toward the luminal walls, for example, but the light intensity at a given point on the luminal wall is affected by reflections, and also by the distance between the irradiating fiber tip and said point. Consequently, fibers have been centered in the lumen using balloons and the like, but the light intensity at the level of the fiber tip, whether it is a point source, sphere, cylinder, etc., is higher than above or below said level. The tip or the balloon can be filled with a diffusively scattering fluid medium, such that light intensity at its surface is more uniform, but losses are high with multiple scattering through long distances in said medium and the transmission efficiency is poor.
Furthermore, such technology is not well suited for delivering the high irradiances required for ablative or coagulative treatments. To ablate in a single light exposure the entire surface area of a lumen affected by a disease, for example, a very high power light source may be required. Treatment of a lumen or hollow organ with light can be done when light requirements are relatively low, for example in photodynamic therapy (PDT), where light is delivered at nonthermal levels to activate a drug, although variable and inconsistent light dosages at the tissue surface remain problematic and may lead to adverse effects, such as strictures, as well as ineffective treatment with recurrences. Alternatively, to ablate superficial tissue in a lumen or hollow organ, a directable optical fiber delivery system, with or without a contact tip, can be used to deliver high irradiances to one section of the affected area at a time. Disadvantages of that segmental approach are that it is time consuming, and it is difficult to avoid overlapping or missed segments.
Limitations in the current technology have limited the application of phototherapy in treatment of lumens and hollow organs. For example, there is the problem of treating Barrett's esophagus (BE) in patients with gastrointestinal reflux disease (GERD), and high grade dysplasia of the esophagus. GERD leads to premalignant changes in the normal squamous epithelium of the distal esophagus. BE is the only known precursor lesion for esophageal adenocarcinoma, the incidence of which has increased by 300 to 500% in the past four decades (Anandasabapathy S, Gastrointest Cancer Res 2:81-84, 2008). Considerable effort has been made over many years to develop PDT for BE. However, difficulties in light delivery as outlined above have contributed to unsatisfactory outcomes, and PDT has not developed into a standard treatment of esophageal disease.
Recently, a balloon radiofrequency device has been developed for treatment of BE and other esophageal diseases. In that device, an array or arrays of electrodes attached to a catheter is positioned at the esophageal surface using a balloon, and the electrode energized to ablate the mucosa. However, disadvantages remain. The surface array design is specific for radiofrequency, and does not enable use of energy in the form of light. With radiofrequency, control over ablation depth must be obtained by choice of power and pulse width. Depth of radiofrequency ablation cannot be controlled as it is with light, where the tissue optical properties of scattering, absorption and anisotropy determine the depth of penetration of a given wavelength. Tissue effects are limited to nonselective thermal destruction in radiofrequency, unlike irradiation with light using wavelengths selectively absorbed by specific tissue components. The electrode arrays must be in full contact with tissue to avoid injury when activated. Furthermore, the tissue-contacting radiofrequency ablation catheters are single use disposables costing approximately $2700 and $1800 for 360° and 90° ablations, respectively, to be used with a $900 disposable sizing balloon. Consequently, radiofrequency ablations performed in an outpatient clinic with the patient under sedation can be nearly as costly as a surgical esophagectomy performed in the operating MOM.
Thus, light is not part of the current armamentarium in treating patients with esophageal disease including BE, despite inherent advantages of light based treatments, either with or without a photodynamic drug, over other less flexible and less precise forms of energy such as radiofrequency.